Professor Giovanna Mallucci and her team have identified two drugs that can block the death of brain cells in mice models of neurodegeneration. This research builds on the earlier breakthrough by the team four years ago.
Liquorice
The study, published in the journal Brain, found that a licensed antidepressant (trazodone) and a compound found in liquorice (dibenzoylmethane — DBM) are capable of reducing brain cell death in mice with prion disease and with frontotemporal dementia. These drugs work by targeting the ‘unfolded protein response’ in cells, which is a natural defence mechanism activated by the accumulation of misfolded proteins in several neurodegenerative diseases including Alzheimer’s.
In 2013, the original research used a single compound to prevent the mechanism of action that shuts down protein production, however, even though the treatment worked in mice models it was found to cause organ damage in humans. It was this approach, however, that was dubbed as the ‘turning point’ for the neurodegenerative field.
Since the initial research, the team tested more than a thousand drugs and found trazodone and DBM were effective at stopping brain cell death in dementia and prion disease. Speaking to BBC News Mallucci said, “Both were very highly protective and prevented memory deficits, paralysis and dysfunction of brain cells. It’s time for clinical trials to see if there’s similar effects in people and put our money where our mouth is. We’re unlikely to cure them completely, but if you arrest the progression you change Alzheimer’s disease into something completely different so it becomes liveable with.”
“We’re excited by the potential of these findings,” added Dr Doug Brown, director of research and development at Alzheimer’s Society. “They show that a treatment approach originally discovered while researching prion disease might also work to prevent the death of brain cells in some forms of dementia. This research is at a very early stage and has not yet been tested in people — but as one of the drugs is already available as a treatment for depression, the time taken to get from the lab to pharmacy could be dramatically reduced.”
This research is being funded by the Medical Research Council, Alzheimer’s Society and Alzheimer Drug Discovery Foundation.